The long-term objectives are to improve our understanding of the pharmacology and toxicology of antitumor agents. A host of environmental substances and therapeutic agents cause pulmonary toxicity. A serious untoward effect of therapy with some antitumor agents is pulmonary toxicity. This project will examine the biochemical and cellular mechanisms responsible for anticancer drug-induced lung toxicity. Particular emphasis will be placed upon evaluating the damage caused by antitumor agents to pulmonary endothelial cell plasma membranes. The aim of this project is to (a) characterize the biophysical and biochemical damage caused by bleomycin and other antitumor agents to the plasma membrane of pulmonary endothelium, (b) quantify the metabolism of bleomycin in various pulmonary cells and the biologic activity of novel metabolites, (c) determine if specific pulmonary cell types localize bleomycin in vivo, (d) evaluate the influence of other antitumor agents on bleomycin-induced lung toxicity and bleomycin pulmonary content and, (e) study the actions of pharmacologic agents that might reduce drug-induced lung toxicity.